The development of a replacement liver for transplant or as an extracorporeal support device is necessary to address the growing liver transplant waiting list and the limited number of available organs. Development of a tissue engineered liver is an exciting possible solution. Integration of hepatocytes and a bile duct system in a three dimensional scaffold where the natural bile canaliculi connect to a bile duct network to support bile flow has not been developed. This research will utilize a novel tissue engineering scaffold with a vascularized three dimensional scaffold structure with compartments for hepatic parenchyma and a biliary system that has been developed. With this scaffold, the factors regulating biliary epithelial cell growth and the mechanism of integration of a bile ducts and bile canaliculi will be identified. The effect of geometry, scaffold materials and growth factors will be studied. This scaffold for a tissue engineered liver will be tested in in-vitro and in-vivo models utilizing mature hepatocytes, small cell hepatocytes, biliary epithelial cells and non-parenchymal cells as cell sources. [unreadable] [unreadable] [unreadable]